For patients suffering from low kidney functions, dialysis is the standard treatment for replicating the function of a normal human kidney. There are two types of dialysis procedures in use, hemodialysis (HD), which circulates the patient's blood through filters located outside the body, and peritoneal dialysis (PD), which uses the peritoneal membrane of the patient's abdominal cavity as a filter to remove toxins via specialized solutions called dialysates.
Compared to HD, PD is a very gentle modality, with its slow corrective action more resembling that of the natural kidney. It is operationally simple, eliminates the need for venipunctures and has lower operational costs. Because the system is not an extracorporeal one, there is no need for a high degree of heparinization, a factor that is especially important in the case of diabetic patients. However, to date HD has continued to dominate in the treatment of End-Stage Renal Disease (ESRD) patients.
In a continuing effort to provide adequate PD treatment for the varied population of patients in need, clinicians have developed a number of different forms of PD modalities collectively known as the Automatic Peritoneal Dialysis (APD) modality. These include the APD modalities of: (i) Continuous Cycling Peritoneal Dialysis (CCPD); a method of performing PD in which an automated cycler performs 4 to 6 regular exchanges every night; (ii) Intermittent Peritoneal Dialysis (IPD); a method of performing PD in hospitals or at home with an automatic cycler two or three times a week for a period of about eight to twenty hours each time; (iii) Nightly Peritoneal Dialysis (NPD); a method of performing nightly peritoneal dialysis at home for patients with high efficiency peritoneal membranes. Such patients do not fare well with long dialysate dwell times.
These modalities all involve an infusion phase, during which the dialysate (normally glucose) is introduced into the peritoneal cavity (Fill), a Dwell phase during which the dialysate is essentially at rest in the peritoneal cavity, and a draining phase following the dwell phase, when the dialysate is expelled from the peritoneal cavity. The majority of the cleansing process takes place during the Dwell. It is this phase that removes the waste products, known as the Ultrafiltrate (UF), from the blood.
With currently available cyclers, there is no evidence-based method to determine when an individual Dwell phase within a treatment should be terminated. In such systems a fixed Dwell time is allocated for every given cycle. This time is adhered to regardless of the status of the UF conditions during that cycle. If the Dwell is allowed to proceed beyond the point when ultrafiltration has ceased, there is a danger of enhanced absorption of Glucose due to the reversal of the flow kinetics. Therefore, it is not uncommon to get glucose transported into the patient body using current cycler technology. This danger is significant during long Dwell periods. To combat this danger significantly more expensive osmotic agents, such as Icodextrine, are being used for long dwell periods. Alternatively, if the Dwell is terminated prematurely the patient does not receive the target dosage.
At least three other major limitations have been recognized with the standard Batch modalities. These are (a) a reduction in the quality of the dialysate during the long Dwell period due to its presence of the UF components; (b) longer than optimum Drain periods that limits the actual time available for the Dwell; and (c) the likelihood of Drain pain at the end of every cycle. This occurs when the cycler attempts to remove fluid from a cavity that is empty before the estimated total drain volume for that cycle has been achieved. This latter issue results from the fact that in the standard cycler, the drain volume is calculated based on an estimate of the expected UF for that cycle and not the actual UF generated during that cycle.
In an attempt to remove these limitations, the modality known as Tidal Peritoneal Dialysis (TPD) was developed. This modality utilizes an initial maximum dialysate fill volume (usually three liters) and periodically, during a long and continuous dwell time, drains a fraction of the infused volume (usually one-third, the tidal volume and known as the Tidal exchange volume) and re-infuses about a similar amount, adjusting for the UF into the patient. Since there may always be fluid present in the cavity, UF occurs during the Drain and subsequent Fill phases. This additional UF adds to that which occurred during the normal Dwell. The net effect is an increase of the effective “Dwell” time, a positive outcome since the Dwell is when the treatment is at its optimum. This methodology ensures that the quality of the dialysis is kept as high as practical within the limitation of the practiced art and that the effective treatment time (Dwell time) is maximized.
The waste transport mechanism that generates the UF is primarily driven by diffusion as a result of the osmotic gradient between the dialysate and the blood. Therefore the attributes of TPD should generate more UF clearance. Unfortunately to date there is no clear evidence that this is the case. See for example Alok Agrawal and Karl D. Nolph, Advantages of Tidal Peritoneal Dialysis, Peritoneal Dialysis International, May 2000, Vol. 20, Suppl. 2, herein incorporated by reference.
TPD consumes more dialysate than any of the other mentioned modalities therefore its cost is higher. The benefit of this additional cost is the potential to reduce pain events since the cavity is only completely emptied once during the treatment. In the other modalities the cavity is emptied multiple times in a treatment and due to the basic nature of prior Drain algorithms, multiple pain events have been recorded during a full treatment.
A number prior systems can perform TPD such as for example European Patent Application No. EP0498382 to Peabody. EP0498382 describes a device that can be used for TPD. The dialysate parameters do not vary and there is no evidence-based method to determine when to perform a Tidal exchange. The frequency and volume exchanged are constant, but the residual volume in the cavity increases over time. This increase in volume was not programmed but is due to the UF that is generated.
U.S. Pat. No. 8,585,634 B2 to Neftel reports a TPD methodology that suggest evidence based exchange times where a mathematical model predicts the times and volumes required. U.S. Patent Publication No. US2012/310056A refines on this model where the inputs rely on either the Personal Dialysis Capacity (PDC) test or the Peritoneal Equilibrium (PET) test. These tests provide transport kinetics of the peritoneum at the time of the test. However, the transport kinetics vary from day to day and cycle by cycle. Moreover the patient's diet and current clinical condition at the time of treatment also affects transport kinetics. Consequently, the numbers generated by such test are only the predicted or expected real time transport properties of the peritoneum at the time of a future treatment. In short they do not provide the actual transport kinetics parameters for real time evidence based determination of any of the exchange parameters. These include but are not limited to exchange volume, exchange time and exchange formulation.
It is common to inject a Last Fill at the end of the TPD cycle, which remains within the patient cavity until the next treatment. This is sometimes referred to as the WET volume. The previously mentioned systems lack the ability to determine if the cavity is truly empty at the final Drain. If the cavity is not empty at the end of the TPD cycle then the actual WET volume will be larger than prescribed resulting in patient discomfort. An example of this approach to TPD is given by U.S. Pat. No. 9,147,045. In this approach, a kinetic model is used to generate a series of UF curves from a limited set of discrete data points collected over a number of separate Dwell periods. The model is used to extrapolate between the discrete data points. The method then selects five individual prescriptions from a suite of possible prescriptions that can generate these curves in accordance to the kinetic model. This method assumes that these five prescriptions meet the individual needs of all patients, which may not be the case since no two patients present identical clinical conditions. The method also assumes that the prescription range is large enough to accommodate any variances that could occur on a daily basis. Furthermore, once the prescription has been initiated no changes can be made during the actual treatment. This method, like in U.S. Publication No. 2012/310056, cannot determine when the cavity is truly empty. Therefore, a high probability exists that the UF is under-estimated and consequently at the next Last Fill the actual volume in the cavity is higher than what is programmed. This combination leads to the clinically dangerous “overfill condition” for the patient.
U.S. Pat. No. 6,228,047 to Dadson and assigned to Newsol Technologies, Inc., assignee of the present application, the contents of which are herein incorporated by reference, discloses a method to address the overfill condition by monitoring the cavity pressure and a method to track and determine the rate of UF production. From these combined methods, it may be possible to arrive at an optimum exchange time if the disclosed methodologies is applied to the Tidal process. However, Dadson assumes that the only pressure rise is due to UF production. This is not the case. For example, patient movement during the night can generate abrupt and large swings in pressure. Also, normal biological functions are superimposed on any observable pressure changes. The method proposed by Dadson gradually reduces the volume of dialysate in the cavity during the Dwell each time the pressure increases beyond some threshold. Dialysate is removed from the cavity and there is no indication of how to replenish this quantity, which is a requirement in TPD. It is desirable to maintain the Dwell volume at the original Fill value and also supply fresh supply dialysate to compensate for the natural dilution by the UF and in an extreme case, Dadson could prematurely empty the cavity. Failure to account and accommodate for these issues prevents Dadson from performing evidence-based Tidal exchange points.